The goal of this project is to investigate the transport of oxygen from blood to striated muscle cells at the level of the capillary network. The adequacy of tissue oxygenation will be assessed from experimental and theoretical perspectives and emphasis will be placed on the role of heterogeneity in capillary network architecture, red blood cell (RBC) hemodynamics and oxygen carriage and release. Experiments will be performed on the retractor muscle of the hamster at rest and during graded contractions. Geometrical measurements on capillaries will include length, diameter, tapering, branching pattern, and spacing with respect to muscle fibers. In addition, we will measure RBC velocity, RBC flux and hematocrit. Oxygen tension distribution in the tissue will be measured with oxygen microelectrodes, and hemoglobin oxygen saturation along the capillaries will be measured spectrophotometrically. The degree of heterogeneity will be assessed from distributions of the above parameters and correlations between various pairs will be examined. The project will be carried out in three stages. First, complete data on oxygen transport in a single capillary and a group of 2 to 3 capillaries will be studied, including a study of interactions between adjacent capillaries. Second, a "tissue module" containing about one-hundred capillaries will be studied at a specified location in the muscle, and a statistical description of oxygen transport will be given for this series of experiments. Third, a description of oxygen transport in a large segment of muscle will be based on studies of tissue modules in different parts of the muscle. Parallel work on mathematical modeling and computer simulation of oxygen transport will also be divided into three stages corresponding to the different levels of muscle organization. The model will explicitly take into account heterogeneous tissue geometry and capillary flow. The results from these studies should allow a more complete understanding of oxygen transport in straited muscle since the transport mechanisms at the level of single capillaries will be linked within the same series of experiments to oxygen transport in tissue modules, and finally, to transport in a large segment of the muscle which possesses the large scale integration characteristics of the whole muscle. This will provide a quantitative description of the correlation between oxygen transport in the microcirculation and macrocirculation.